The film was one of the first to present an authentic and sympathetic view of the Native Americans. In his review of the DVD release of Fort Apache in 2012, New York Times movie critic Dave Kehr called it "one of the great achievements of classical American cinema, a film of immense complexity that never fails to reveal new shadings with each viewing ... among the first pro-Indian westerns" that portrays the Native Americans with "sympathy and respect".[7]

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After the American Civil War, highly respected veteran Captain Kirby York (John Wayne) is expected to replace the outgoing commander at Fort Apache, an isolated U.S. cavalry post. York had commanded his own regiment during the Civil War and was well-qualified to assume permanent command. To the surprise and disappointment of the company, command of the regiment was given to Lieutenant Colonel Owen Thursday (Henry Fonda). Thursday, a West Point graduate, was a general during the Civil War. Despite his Civil War combat record, Lieutenant Colonel Thursday is an arrogant and egocentric officer who lacks experience dealing with native Indians.

Accompanying widower Thursday is his daughter, Philadelphia (Shirley Temple). She becomes attracted to Second Lieutenant Michael Shannon O'Rourke (John Agar), the son of Sergeant Major Michael O'Rourke (Ward Bond). The elder O'Rourke was a recipient of the Medal of Honor as a major with the Irish Brigade during the Civil War, entitling his son to enter West Point and become an officer. However, the class-conscious Thursday forbids his daughter to see someone he does not consider a gentleman.

When there is unrest among the Apache, led by Cochise (Miguel Inclan), Thursday ignores York's advice to treat the natives with honor and to remedy problems on the reservation caused by corrupt Indian agent Silas Meacham (Grant Withers). Thursday's inability to deal with Meacham effectively, due to his rigid interpretation of Army regulations stating that Meacham is an agent of the United States government and therefore entitled to Army protection (despite his own personal contempt for the man), coupled with Thursday's prejudicial and arrogant ignorance regarding the Apache drives the Indians to rebel. Eager for glory and recognition, Thursday orders his regiment into battle on Cochise's terms, a direct charge into the hills, despite York's urgent warnings that such a move would be suicidal. Thursday relieves York and orders him to stay back, replacing him with Captain Sam Collingwood (George O'Brien).

Following Thursday's orders, York spares the younger O'Rourke from battle. Thursday's entire command is nearly wiped out, but a few soldiers manage to escape back to the ridge where Captain York is positioned. Thursday himself survives but then returns to die with the last of his trapped men. Cochise spares York and the rest of the detachment because he knows York to be an honorable man.

Subsequently, now Lieutenant-Colonel Kirby York commands the regiment. Meeting with correspondents, he introduces Lt. O'Rourke, now married to Philadelphia Thursday. A reporter asks Colonel York if he has seen the famous painting depicting "Thursday's Charge." York, about to command a new and arduous campaign to bring in the Apaches, while believing that Thursday was a poor tactician who led a foolhardy and suicidal charge, says it is completely accurate and then reminds the reporters that the soldiers will never be forgotten as long as the regiment lives.

Crowther, Bosley (June 25, 1948). "Fort Apache, RKO Western, With Fonda, Wayne and Temple, Bill at Capitol". The New York Times. In his contemporary review, Crowther writes "apparent in this picture, for those who care to look, is a new and maturing viewpoint upon one aspect of the American Indian wars. For here it is not the "heathen Indian" who is the "heavy" of the piece but a hard-bitten Army colonel, blind through ignorance and a passion for revenge. And ranged alongside this willful white man is a venal government agent who exploits the innocence of the Indians while supposedly acting as their friend."